Metabolism

Propofol is rapidly metabolized in the liver by conjugation to glucuronide and sulfate^[6] to produce water-soluble compounds, which are excreted by the kidneys.^[6] Less than 1% of propofol is excreted unchanged in urine, and only 2% is excreted in feces.^[6] The metabolites of propofol are not thought to be active. Because clearance of propofol exceeds hepatic blood flow, extrahepatic metabolism or extrarenal elimination has been suggested. Extrahepatic metabolism has been confirmed during the anhepatic phase of patients receiving a transplanted liver.^{[7] [8]} The lungs seem to play an important role in this extrahepatic metabolism. They are responsible for approximately 30% of the uptake and first-pass elimination after a bolus dose.^[9] During a continuous infusion of propofol there is a 20% to 30% decrease in propofol concentration measured across the lung in humans and a higher concentration of the metabolite 2,6-diisopropyl-1,4-quinol on the arterial side of the circulation.^[10] Other sites of propofol metabolism are also likely. During in vitro studies with human kidney and small intestine, microsomes in these tissues demonstrated an ability to form propofol glucuronide.^[11] Propofol itself results in a concentration-dependent inhibition of cytochrome P450 and thus may alter the metabolism of drugs dependent on this enzyme system (e.g., opiates).^[12]